The emerging era of personalized therapy in squamous cell carcinoma of the head and neck

Pryor, David; Solomon, Benjamin; Porceddu, Sandro

doi:10.1111/j.1743-7563.2011.01420.x

Cited by 19 publications

(20 citation statements)

References 115 publications

(138 reference statements)

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“…All patients with HPV DNA + OSCC may not benefit from intensified treatment, and to decrease the severe side-effects, it has been proposed to reduce treatment for this group. However, since a significant proportion of patients with HPV DNA + OSCC have a poor clinical outcome, additional predictive markers are needed, before introducing a possible de-escalation of treatment[9,10]. …”

Section: Introductionmentioning

confidence: 99%

HLA Class I and II Expression in Oropharyngeal Squamous Cell Carcinoma in Relation to Tumor HPV Status and Clinical Outcome

et al. 2013

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HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16INK4a and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16INK4a overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.

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Section: Introductionmentioning

confidence: 99%

HLA Class I and II Expression in Oropharyngeal Squamous Cell Carcinoma in Relation to Tumor HPV Status and Clinical Outcome

et al. 2013

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“…HNSCC is an aggressive disease characterized by extensive locoregional invasion and cervical lymph node metastasis (1,2). Overexpression of EGFR is common in HNSCC and correlates with enhanced invasion and nodal involvement (3–6).…”

Section: Introductionmentioning

confidence: 99%

Ableson kinases negatively regulate invadopodia function and invasion in head and neck squamous cell carcinoma by inhibiting an HB-EGF autocrine loop

et al. 2012

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Head and neck squamous cell carcinoma (HNSCC) has a proclivity for locoregional invasion. HNSCC mediates invasion in part through invadopodia-based proteolysis of the extracellular matrix (ECM). Activation of Src, Erk1/2, Abl and Arg downstream of epidermal growth factor receptor (EGFR) modulates invadopodia activity through phosphorylation of the actin regulatory protein cortactin. In MDA-MB-231 breast cancer cells, Abl and Arg function downstream of Src to phosphorylate cortactin, promoting invadopodia ECM degradation activity and thus assigning a pro-invasive role for Ableson kinases. We report that Abl kinases have an opposite, negative regulatory role in HNSCC where they suppress invadopodia and tumor invasion. Impairment of Abl expression or Abl kinase activity with imatinib mesylate enhanced HNSCC matrix degradation and 3D collagen invasion, functions that were impaired in MDA-MB-231. HNSCC lines with elevated EGFR and Src activation did not contain increased Abl or Arg kinase activity, suggesting Src could bypass Abl/Arg to phosphorylate cortactin and promote invadopodia ECM degradation. Src transformed Abl−/−/Arg−/− fibroblasts produced ECM degrading invadopodia containing pY421 cortactin, indicating that Abl/Arg are dispensable for invadopodia function in this system. Imatinib treated HNSCC cells had increased EGFR, Erk1/2 and Src activation, enhancing cortactin pY421 and pS405/418 required for invadopodia function. Imatinib stimulated shedding of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) from HNSCC cells, where soluble HB-EGF enhanced invadopodia ECM degradation in HNSCC but not in MDA-MB-231. HNSCC cells treated with inhibitors of the EGFR invadopodia pathway indicated that EGFR and Src are required for invadopodia function. Collectively our results indicate that Abl kinases negatively regulate HNSCC invasive processes through suppression of an HB-EGF autocrine loop responsible for activating a EGFR-Src-cortactin cascade, in contrast to the invasion promoting functions of Abl kinases in breast and other cancer types. Our results provide mechanistic support for recent failed HNSCC clinical trials utilizing imatinib.

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“…A newer agent, fluorine-18 fluoroazomycin arabinoside (18FAZA), has the advantage of a faster blood clearance than FMISO, resulting in improved target-to-background contrast and should be further studied in clinical trials [43,44]. Furthermore, recent results have suggested a potential benefit of the hypoxic radiosensitizer tirapazamine for selected HNC patients who were at high risk for locoregional failure (smokers and patients with HPV negative tumors), had evidence of hypoxia on functional imaging and received high-quality radiotherapy [47–49]. …”

Section: The Role Of Novel Pet Tracers For Hncmentioning

confidence: 99%

FDG-PET,a Complementary Modality to Computed Tomography in Radiotherapy Target Volume Delineation for Head and Neck Cancer

Bar‐Ad

Shi²,

Tuluc³

et al. 2012

J Nucl Med Radiat Ther

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Objectives The objective of the current review was to use published data to assess the role of [18F] fluorodeoxyglucose-positron emission tomography (FDG-PET) as a complementary modality to computed-tomography (CT) in radiotherapy target volume delineation for head and neck cancer (HNC). Methods Studies were identified by searching PubMed electronic databases. Both prospective and retrospective studies were included. Information regarding the role of FDG-PET for radiotherapy target volume delineation for HNC was analyzed. Results FDG-PET is a promising tool for improving radiotherapy target volume delineation by defining a metabolically active biological target volume (BTV). The use of novel PET tracers representing properties such as hypoxia, protein synthesis and proliferation remain to be better characterized. Conclusions The role of FDG-PET for radiotherapy target volume delineation for patients with HNC is expanding and should be further evaluated in clinical trials.

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The emerging era of personalized therapy in squamous cell carcinoma of the head and neck

Cited by 19 publications

References 115 publications

HLA Class I and II Expression in Oropharyngeal Squamous Cell Carcinoma in Relation to Tumor HPV Status and Clinical Outcome

HLA Class I and II Expression in Oropharyngeal Squamous Cell Carcinoma in Relation to Tumor HPV Status and Clinical Outcome

Ableson kinases negatively regulate invadopodia function and invasion in head and neck squamous cell carcinoma by inhibiting an HB-EGF autocrine loop

FDG-PET,a Complementary Modality to Computed Tomography in Radiotherapy Target Volume Delineation for Head and Neck Cancer

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